A major function of the eccrine sweat gland is thermoregulation. The importance of this function is underscored by human disorders in which the eccrine glands are lost or are non-functional. These conditions can be life threatening during infancy and childhood. In spite of the clinical significance of the eccrine glands, they have not been well studied. In order to understand how they develop, we have begun by conducting a detailed characterization of the gross morphological and histological changes that occur from the initiation of patterning and morphogenesis through the completion of differentiation in the mouse eccrine gland. Information from these studies will provide a critical foundation for understanding the effects of mutations affecting eccrine gland development. Recent data from this laboratory has implicated the hedgehog (hh) signaling pathway as a key molecular regulator of eccrine gland morphogenesis. This pathway has already been shown to be critical for the normal development of other appendages, and its inappropriate regulation can lead to basal cell carcinomas, the most common form of skin cancer. We propose to delineate the roles of several hh signaling components in eccrine gland development. [unreadable] [unreadable]